Ki: 8.6 nM for HT-29 cells
SR 48692 is a nonpeptide neurotensin antagonist.
Neurotensin is a tridecapeptide and is distributed in both the central and peripheral nervous systems. Neurotensin shows a wide spectrum of biological activities resulting in fulfilling a dual function as a neurotransmitter/neuromodulator in the brain and working as a hormone/cellular mediator in peripheral tissues.
In vitro: SR 48692 was found to inhibit the binding of [3H]- or [125I]-neurotensin to membrane preparations from mouse brains and HT-29 cells. In HT-29 cells, SR 48692 also antagonized the neurotensin-induced mobilization of intracellular calcium, which was consistent with previous findings. Moreover, in rat cerebellar slices, SR 48692 could block the cyclic GMP level increase in a dose-dependent manner [1].
In vivo: SR 48692 could antagonize the increase in rat brain mesolimbic dopamine turnover which was induced by the systemically active neurotensin peptide EI. Whereas, SR 48692 did not antagonize EI-induced decrease in mouse body temperature and spontaneous locomotor activity [1].
Clinical trial: In a clinical study, SR 48692 was used to assess the effect of endogenous neurotensin on lower oesophageal sphincter function. Results showed that SR 48692, however, had no effect on oesophageal motility in humans [2].
References:
[1] Pugsley TA,Akunne HC,Whetzel SZ,Demattos S,Corbin AE,Wiley JN,Wustrow DJ,Wise LD,Heffner TG. Differential effects of the nonpeptide neurotensin antagonist, SR 48692, on the pharmacological effects of neurotensin agonists. Peptides.1995;16(1):37-44.
[2] Zerbib F,Piche T,Charles F,Galmiche JP,Bruley des Varannes S. SR 48692, a specific neurotensin receptor antagonist, has no effect on oesophageal motility in humans. Aliment Pharmacol Ther.2004 Apr 15;19(8):931-9.
